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Vitamin B3 treatment for ataxia shows promise in first human trial

1 May 2014

A form of vitamin
B3 has shown early promise against Friedreich’s ataxia, a debilitating
degenerative disease with no treatment or cure, in the first human trial of the
treatment involving UCL researchers.

Friedriech’s
ataxia is thought to be caused by a lack of frataxin, a protein important in
regulating iron levels within cells. Frataxin deficiency causes iron overload
in mitochondria, the ‘batteries’ of cells, and problems regulating free
radicals within cells. These damaging effects lead to cellular death.

As the damage
builds up, people with the condition suffer from progressively worsening
symptoms including problems walking, talking, swallowing, seeing and hearing.
Many patients are wheelchair-bound and unable to live independently a decade or
two after symptoms appear and often die of heart disease within 35 years.

In a
collaborative effort, researchers from UCL and Imperial College London gave
patients a form of vitamin B3 called nicotinamide in much higher doses than
found in vitamin supplements. The vitamin has been shown to increase frataxin
levels in the lab, but this was the first test in ataxia patients. The
treatment had minimal side effects and increased patients’ frataxin levels to
match those of ataxia carriers who do not experience symptoms.

Whether restoring
frataxin levels will slow or halt the progress of the disease is still unclear,
as the protein’s precise role in the disease is not yet fully understood. Yet
as carriers do not suffer from symptoms, restoring frataxin levels to those
seen in carriers is a significant step.

“We are excited
by the prospects of nicotinamide potentially being developed into a treatment,”
said Dr Paola Giunti of the UCL Ataxia Centre, who was instrumental in the
trial design and patient recruitment. “We have developed extensive expertise in
trials in such a rare disorder, Friedreich’s ataxia and assembled the largest
cohort of patients in Europe and thus we are in an ideal position to ensure the
success of trials such as this. However it is important to remember that we
still need to conduct further trials to confirm the safety over a longer time
and to see whether the increase in frataxin actually results in improvements
for patients. We are extremely grateful to all the patients who have taken part
in this important pilot trial.”

Finding a cure for Friedreich’s ataxia is what every researcher in the field dreams about. We're absolutely thrilled by our preliminary results and the hope it offers for the future of patients with this devastating condition and their families.

Dr Vincenzo Libri (UCL Leonard Wolfson Experimental Neurology Centre)

Lead author Dr Vincenzo Libri, Head of the Leonard Wolfson Experimental
Neurology Centre at UCL and former Head of Clinical Studies at the NIHR/Welcome Trust Imperial College Clinical Research Facility, said: “Finding a cure for Friedreich’s ataxia
is what every researcher in the
field dreams about. We're absolutely thrilled by our preliminary results
and
the hope it offers for the future of patients with this devastating
condition
and their families.”

Professor Richard
Festenstein of Imperial College London said: “These results are very
encouraging and importantly offer the prospect of a future treatment for this
incurable condition. Further studies are needed to determine the safety of
high-dose nicotinamide with long-term administration and whether it can
increase frataxin levels when given for longer periods. Then we need to know if
this will prevent further clinical decline in patients with Friedreich’s
ataxia. The study is also exciting because it provides proof-of-concept that
aberrant gene silencing can be overcome in humans using an epigenetic*
modifier.”

The trial was
supported by the UK Medical Research Council, Ataxia UK, and the UK National
Institute for Health Research (NIHR). Sue Millman, CEO of Ataxia UK, said: “We
are really proud to have supported the basic science for this hugely exciting
trial and to have moved the research forward to a human trial with such
positive early findings. This study was a truly collaborative effort involving
ataxia charities in four countries and a number of other funding bodies all
recognizing the importance of the study. We now need to push forward towards a
larger trial which we hope can eventually be translated into a treatment for
patients. That is our goal.”

*Epigenetic refers to how the gene is
'packaged' within the nucleus. DNA wraps around histone proteins to form a
beads-on-a-string pattern known as chromatin. The ends of the histone proteins
are normally labelled as 'active' but at the Friedreich’s ataxia gene this
‘active’ labelling is removed so that the gene is abnormally switched off.
Nicotinamide prevents these labels from being removed, switching the gene back
on.